Discovery of novel Hsp90 C-terminal domain inhibitors that disrupt co-chaperone binding

Heat shock protein 90 (Hsp90) is an essential molecular chaperone that performs vital stress-related and housekeeping functions in cells and is a current therapeutic target for diseases such as cancers. Particularly, the development of Hsp90 C-terminal domain (CTD) inhibitors is highly desirable as inhibitors that target the Nterminal nucleotide-binding domain may cause unwanted biological effects. Herein, we report on the discovery of two drug-like novel Hsp90 CTD inhibitors by using virtual screening and intrinsic protein fluorescence quenching binding assays, paving the way for future development of new therapies that employ molecular chaperone inhibitors.

Automated summary

Heat shock protein 90 (Hsp90) is a crucial molecular chaperone in cells, serving important functions in stress response and maintenance, and is currently targeted for cancer treatment. Two novel drug-like Hsp90 CTD inhibitors were discovered through virtual screening and protein fluorescence quenching assays, providing a potential avenue for developing new therapies using molecular chaperone inhibitors.